PROJECT SUMMARY Neisseria gonorrhoeae (Gc) is the sole causative agent of the sexually transmitted infection gonorrhea. The rapid raise in antibiotic resistance coupled with a recent sharp increase in reported cases in the U.S. have made this organism a target for the CDC, WHO and NIH. This proposal will focus on the Gc Type IV pilus (T4p), which is an essential colonization and virulence factor. We will determine how the T4p helps to protect Gc from polymorphonuclear leucocyte (PMN) killing by altering iron homeostasis within the bacterial cell. Additionally, we will perform a small molecule screen to identify molecules that can inhibit a protease necessary for Gc T4p elaboration to develop novel pharmacologic agent for research and set the stage for the possibility for new types of compounds that act against Gc and possibly other pathogenic bacteria.